Directional dynamics in the entorhinal cortex of male mice driven by behavioral constraints

The medial entorhinal cortex of rodents contains a variety of functionally-defined cell types, including grid and head direction cells. While evidence indicates that functional types are not associated with clear molecular footprints, the factors that define them remain unclear. By comparing neural recordings in male mice exploring the same environment either freely or head-fixed to an autonomous-driving cart, we here show that, for a substantial portion of neurons, the head direction functional identity is dynamic, likely emerging through self-organization. Approximately half of free-foraging head direction cells reversibly lost their tuning during assisted navigation, while other neurons gained directional tuning, especially in environments enriched with sensory cues. This adaptive process is experience-dependent, progressively sharpening and stabilizing directional representations, while also integrating a spatial component. Our findings reveal a remarkable flexibility of entorhinal representations, demonstrating their capacity to reorganize and adapt based on how animals interact with their environment.